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Lee, Changwook
Structural Biology of Cellular Biochemistry Lab
Research Interests
  • Cell biology, structural biology, protein biochemistry, membrane biology, cancer biology

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Rogdi Defines GABAergic Control of a Wake-promoting Dopaminergic Pathway to Sustain Sleep in Drosophila

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Title
Rogdi Defines GABAergic Control of a Wake-promoting Dopaminergic Pathway to Sustain Sleep in Drosophila
Author
Kim, MinjongJang, DonghoonYoo, EunseokOh, YangkyunSonn, Jun YoungLee, JongbinKi, YoonheeSon, Hyo JinHwang, OnyouLee, ChangwookLim, ChunghunChoe, Joonho
Issue Date
2017-09
Publisher
NATURE PUBLISHING GROUP
Citation
SCIENTIFIC REPORTS, v.7, pp.11368
Abstract
Kohlschutter-Tonz syndrome (KTS) is a rare genetic disorder with neurological dysfunctions including seizure and intellectual impairment. Mutations at the Rogdi locus have been linked to development of KTS, yet the underlying mechanisms remain elusive. Here we demonstrate that a Drosophila homolog of Rogdi acts as a novel sleep-promoting factor by supporting a specific subset of gamma-aminobutyric acid (GABA) transmission. Rogdi mutant flies displayed insomnia-like behaviors accompanied by sleep fragmentation and delay in sleep initiation. The sleep suppression phenotypes were rescued by sustaining GABAergic transmission primarily via metabotropic GABA receptors or by blocking wake-promoting dopaminergic pathways. Transgenic rescue further mapped GABAergic neurons as a cell-autonomous locus important for Rogdi-dependent sleep, implying metabotropic GABA transmission upstream of the dopaminergic inhibition of sleep. Consistently, an agonist specific to metabotropic but not ionotropic GABA receptors titrated the wake-promoting effects of dopaminergic neuron excitation. Taken together, these data provide the first genetic evidence that implicates Rogdi in sleep regulation via GABAergic control of dopaminergic signaling. Given the strong relevance of GABA to epilepsy, we propose that similar mechanisms might underlie the neural pathogenesis of Rogdi-associated KTS.
URI
https://scholarworks.unist.ac.kr/handle/201301/22709
URL
https://www.nature.com/articles/s41598-017-11941-3
DOI
10.1038/s41598-017-11941-3
ISSN
2045-2322
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SLS_Journal Papers
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